| Therapeutic proteins are one of the most important and rapidly growing segments of the pharmaceutical market, with annual sales of over US$35 billion in 2005. Paul Martin of Nautilus Biotech reports on recent developments in oral drug delivery of therapeutic proteins
Despite the increasing predominance of therapeutic proteins on the market, producers of first generation protein drugs currently face a number of important problems. One example is patent expiries on several blockbuster products and the competition from small molecule alternatives and biogenerics. In addition, the need for better clinical performance, as well as product life cycle management, is motivating the search for products with improved characteristics (for example, longer half-life in serum) as well as alternatives to injection as the main route of administration.
ESTABLISHED STRATEGIES FOR ORAL DELIVERY
In order to develop new routes of administration, heavy investment has been made in pulmonary, nasal and oral drug delivery. In particular, oral delivery of therapeutic proteins has long been a major objective of the biotech industry, as this would significantly increase the ease of administration, and would allow more tailored dosing regimes. These in turn could greatly improve patient compliance. However, effective oral delivery of a protein will require overcoming a number of major challenges, including: the need to ensure the protein is protected from degradation by the specific proteases encountered throughout the oral delivery pathway (for instance, oral mucosa, saliva, stomach and intestine), as well as the low pH in the stomach and the need for epithelial transport from the intestinal lumen into the blood (1). At the same time, any drug that enters the bloodstream will need to maintain a good PK profile (that is, half-life in serum). |
